DESCRIPTION: (Principal Investigator's) Over the years, there has been an enormous emphasis on asymmetric synthesis in organic chemistry. In this context, the discovery and development of efficient reactions has been the arena of major research activities. The effectiveness of such new synthetic processes is traditionally evaluated by their utility in the synthesis of an array of organic molecules that are found in nature. From synthesis of biologically important natural products to synthesis of various enzyme inhibitors or receptor agonists or antagonists, there is a growing need for general strategies for enantioselective bond construction in a stereopredictable fashion. In addition, the growing isolation and characterization of many complex natural products with important biological functions as well as the increasing understanding of many complex human diseases at the molecular level, demands the development of newer synthetic methodologies. The questions and concepts of molecular binding, structure-function relationship, reactivity, and intermolecular as well as intramolecular bonding interactions all are at the forefront of organic chemistry. Asymmetric synthesis is now faced with new challenges and opportunities. Quite naturally, expansion of basic knowledge, development of newer asymmetric synthesis and understanding of various asymmetric reactions at the molecular level are of enormous significance. In this context, my plan is to design and develop various ligand assisted stoichiometric and catalytic asymmetric syntheses and demonstrate their utility in the synthesis of natural and unnatural organic molecules. The specific aims of the present proposal are: (a) to perform in-depth mechanistic studies of asymmetric ester enolate aldol reactions and asymmetric catalytic hetero Diels-Alder reactions; (b) to utilize the obtained molecular insight to further develop these reactions as well as discover new asymmetric processes; (c) to demonstrate the utility of such asymmetric reactions in the synthesis of various biologically important molecules, such as madumycin. Besides the broad range of scope and generality, this line of research will provide excellent opportunities to teach and train graduate and undergraduate students in the laboratory.